- Email: [email protected]
61 Late toxicity after adjuvant radiochemotherapy for gastric adenocarcinoma
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September 13-16
58 Identification of Predictive Factors of Response to Radiation Therapy in Patients with Carcinoma of the Cervix C. Doll1, P. Craighead I, S. Lees-Miller 2, D. Demetrick 2, T. Magliocco 2 Torn Baker Cancer Centre, University of Calgary, Calgary, AIbertal ; University of Calgary, Calgary, Alberta 2 corinned@cancerboard, ab. ca
Purpose: To identify predictive factors for tumour response after radiation therapy in patients with carcinoma of the cervix, and to correlate the tumour expression of molecular markers with local control, disease-free and overall survival. Materials and Methods: This is a retrospective study of patients who completed radical radiotherapy alone for cervix cancer between 1986 and 1996. One hundred and ninety-two patients were identified. Patient and turnout data, as well as treatment parameters and outcomes, were obtained from patient records. One hundred and four patients had pretreatment tumour specimens available for analysis. Tissue microarrays were constructed from these tumour blocks. Immunohistochemica~ assays were performed with marker expression determined independently by two physicians blinded to clinical outcome. To date, immunostaining has been performed for detection of COX-2, GLUT-l, EGFR, involucrin, p53, and c-erbB-2 expression. Further immunostaining on hypoxia markers, as well as DNA repair markers, is underway. For analysis purposes, samples will be divided into radiosensitive and radioresistant groups based on clinical response, and differences in marker expression will be investigated. Results: Median follow-up was eight years. Mean patient age was 54 years, and median clinical tumour size was 5cm. The majority of patients (78%) had Stage I or II disease. Mean radiation dose to point A was 8165 cGy. Pelvic recurrence occurred in 28% of patients, with a median time to recurrence of 16 months. Distant metastases were seen in 18% of patients. Positive immunostainlng for GLUT-1 was seen in 90% of tumour specimens, COX-2 positive staining in 85%, EGFR positive staining in 67%, and p53 positive staining in 18% of specimens. Only 0.5% of tumour specimens stained positive for c-erbB-2 expression. We are currently analyzing expression profiling with clinical outcome parameters, results of which will be available for presentation. 59 Development of a Three-Dimensional Anisotropic Pelvic Lymph Node Clinical Target Volume Using Magnetic Resonance Lymphography with Ferumoxtran-lO R. Dinniwell, P. Chan, M. Haider, A. Fyles, M. Milosevic Princess Margaret Hospital, University of Toronto, Toronto, Ontario Rob. Dinniwell@rm p. uhn. on. ca
Purpose: To develop three-dimensional anisotropic scale factors for the use of the pelvic vasculature as a surrogate for lymphatic target volume definition using Magnetic Resonance Imaging (MRI) with an ultra-small superparamagnetic iron oxide that delineates phagocytotic activity within lymph nodes. Methods: A single centre trial was undertaken in patients with genitourinary and gynaecological malignancies. All patients underwent pre- and post- contrast MRI studies over two consecutive days. Ferumoxtran-10 (Combidex(r): Advanced Magnetics, Inc, Cambridge, MA) was administered on the first day. Axial images were obtained at 3mm intervals through the pelvis. Lymph node frequency and location relative to the adjacent vascular segments was analyzed. Each lymph node was divided into 0.5 x 0.5 x 3mm 3 nodal voxels. The radial position and minimal distance between the centre of each nodal voxel and the closest artery or vein (in three-dimensions) was calculated. Results: Twenty-five patients have been analyzed. A mean of 24 lymph nodes (range 18 to 34) were identified per patient. The maximum distance of the lymph nodes from the closest vessel was between 2.5 and 30ram, with a mean distance of
CARO 2 0 0 6
7.5mm. Anisotropic margins with radial divisions of 60 and 90 degrees revealed significant differences in the anterior, posterior, medial and lateral distribution of the lymph nodes along each of the pelvic vascular segments. The nodal volumes were distributed with: 47% anterior, 11% posterior, 17% medial and 25% lateral to the common lilac vessels; 19% anterior, 32% posterior, 23% medial and 26% lateral to the external lilac vessels; and 38% anterior, 7% posterior, 34% medial and 21% lateral to the internal lilac vessels. Conclusions: The development of anisotropic scale factors specific to the pelvic vasculature and the adjacent lymphatics will facilitate improved coverage of the critical lymph node targets using their corresponding vascular segments as surrogates. 6O Improving Image-Guided Target Localization through Deformable Registration K. Brock, M. Hawkins, C. Eccles, J. Moseley, D. Moseley, L. Dawson Princess Margaret Hospital, University of Toronto, Toronto, Ontario kristy, brock@rinD, uh n. on. ca
Purpose: To quantify the improvements in online target localization using deformable image registration and kV conebeam CT (CBCT). Methods and Materials: Twelve patients treated under a Research Ethics Board approved hypo-fractionated liver protocol were imaged using CBCT at each of the six treatment fractions. The images were imported into the treatment planning software and aligned, using rigid registration, to best fit the liver into the contours previously drawn on the CT scan. The liver was then contoured on each CBCT image. Deformable registration was performed to align the liver, defined'on the CT image, to each CBCT image, using MORFEUS, a biomechanical model based deformable image registration algorithm. The tumour, defined on the planning CT, was mapped onto the CBCT, through the deformable registration, which accounts for the biomechanical relationship between the liver and the tumour. The displacement of the centre of mass (COMT) of the turnout was computed. Results: The mean (SD) displacement of the COMT following deformable registration across all 12 patients was -0.03 (0.10), -0.01 (0.16), and -0.02 (0.14) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COMT was 0.36, 0.65, and 0.57cm in the LR, AP, and SI directions, respectively. Ten percent of the treatment fractions had a COMT displacement of greater than 3mm in one direction and 33% of patients had at least one fraction with a displacement of greater than 3ram. COMT displacement loosely correlated with mean liver deformation (R2 = 0.30, 0.51, and 0.13 in the LR, AP, and SI directions, respectively). Conclusions: Rigid registration of the liver volume between CT and CBCT localizes the tumour to within 3mm for the majority (66%) of patients; however, larger offsets in tumour can be observed if liver deformation is evident during rigid registration. 61 Late Toxicity After Adjuvant Radiochemotherapy for Gastric Adenocarcinoma B. Wysocka, Z. Kassam, G. Lockwood, J. Brierley, L. Dawson, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wvsocka@rmD. uhn. on. ca
Purpose: To assess late toxicity following adjuvant therapy for resected gastric cancer. Methods: A retrospective review of radiation dose volume histograms (DVHs) for liver and kidneys and of late toxicity (clinical or biochemical) was performed for gastric cancer patients who received adjuvant radiochemotherapy between 2000 and 2005.
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Results: The records of 80 patients were reviewed. The mean age was 58 years (range 22-75), with 53 (66%) males. Stage distribution was: IB - 13 (16%), II - 32 (40%), I I I A - 24 (30%), IIIB - 4 (9%) and IV - 7 (9%). 45 Gy in 25 fractions was delivered with a conformal technique. Bolus 5FU and folinic acid was given in 69; 11 received investigational 5FU and Cisplatin in escalating dose. All treatment was completed in 56 (70%) patients; nine (11%) did not complete radiotherapy and 22 (27.5 %) had chemotherapy dose omissions. Median follow up is 30 months (range 6-62). At two years, overall survival was 84% (95% CI 73%-90%). Mean V30 (volume receiving 30 Gy or more) for liver was 31%, whereas mean V22.5 was 31%, 18% and 25% for left kidney, right kidney and combined volume of both kidneys, respectively. Mean of means was 22 Gy for liver and 15 Gy for kidneys. Late toxicity occurred in six patients at nine to 53 months following treatment: bowel obstruction/ perforation (2) and anastomotic stricture (4), in volumes treated to 45 Gy. There was no clinical renal or hepatic toxicity. Grade 1 (CTCAE v3.0) creatinine elevation was observed in eight (10%) patients; at least one liver test was altered in 22 (27.5%): grade 1-17; 2-4; 3-1. Abnormal bloodwork occurred nine days to 55 months after treatment and did not correlate with higher kidney and liver doses. Conclusions: In our cohort of patients treated with radiochemotherapy, small bowel and anastomotic toxicity prevailed, with no clinical renal or hepatic toxicity observed. Biochemical renal and hepatic changes were not related to clinical toxicity or dose delivered. 62 Upper Abdominal Organ Motion During Conformal Radiotherapy for Gastric Carcinoma B. Wysocka, Z. Kassam, G. Lockwood, L. Dawson, J. Brierley, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wysocka@rmp. uh n. on. ca
Aim: To determine respiratory and interfraction organ motion in gastric cancer patients receiving adjuvant radiochemotherapy. Methods: Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained on 17 patients in weeks one, three and five of post-operative gastric cancer treatment with BodyFix immobilization. Images from 138 scans were registered to the planning CT using automated bone registration. Volumes of interest (VOI) were contoured [right (RK) and left (LK) kidney, liver (L), stomach (S), pancreas (P), celiac axis (C) and porta-hepatis (PH) and the centre of mass of each organ was identified as a point of interest (POI). POIs were also placed at dome of diaphragm (D) and splenic hilum (SH). Organ motion was measured using the difference of POI position in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Inhale and exhale positions at each time point were used to determine respiratory motion. Interfractional motion at weeks one, three and five was determined and compared to planning (FB) or week one (I, E) scan. Results: Respiratory motion is maximal in the CC direction with median absolute displacements of: SH 24, LK 20.8/RK 19.6, D 20.5, L 16.1, S 15.5, P 15.1, PH 12 and C 3.Smm. In the AP direction, the greatest median displacement was: SH 9.4ram and in the RL direction motion was less (maximal for PH and SH, 2.9ram). Median absolute respiratory displacement for all organs was: 17.5mm CC, 5.9mm AP, and 2.7ram RL. Median interfraction displacement (range, mm) for all organs was: CC 4.6 (0-38), AP 2.2 (0-20.5), RL 2.2 (0-37.1) in FB; CC 6.3 (0-36), AP 3.8 (0.1-16.6), RL 2.5 (0-19.6) in I and CC 6 (046), RL 2.6 (0-19.4), AP 2.3 (0-12.9) in E. Conclusions: 1) Organ motion in upper abdomen can be substantial and should be incorporated in the planning target volume for conformal or IMRT planning. 2) Median interfraction organ position variability is substantial and similar for all phases of breathing.
September 13-16
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63 Primary and Adjuvant Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase I / I I Study with Long Term Outcome A.M. Brade, C. Townsley, C. Brezden-Masley, D. Hedley, M. MacLean, S. Gallinger, G, Pond, A.M. Oza, M.J. Moore, J. Brierley Princess Margaret Hospital, University of Toronto, Toronto, Ontario anthony, brade@rm p. uhn. on. ca
Objectives: Gemcitabine (G) is active against pancreatic carcinoma and is a potent radiosensitizer. We present extended follow-up data from a Phase I/II study of patients treated with combination Gemcitabine and radiation (GRT). Methods: Eligible patients had either LA or high risk resected (R) pancreatic cancer (positive nodes or positive margin). Twenty-eight were enrolled in a Phase I study of increasing doses of radiotherapy (35 Gy [n=7]/43.75 Gy [n=11]/52.5 Gy (n=10) given over 4, 5 or 6 weeks, respectively in 1.75 Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently 35 were treated with induction G 1000 rag/m2 7/8 weeks followed by concurrent bi-weekly Gemcitabine (40 mg/m2) with 52.5 Gy (30 fractions of 1.75 Gy over six weeks). In total there were 63 patients (30 LA and 33 R) treated between March 1999 - July 2001. Results: In the LA population the best response observed was CR - 1, PR - 2, SD - 10, PD - 10. GRT was not delivered to eight patients due to progression on G alone (n=5) or patient request (n=3). By intent to treat analysis, the median survival in LA disease was 14.5 months and two-year survival was 17%. In the resected population the median time to progression was 8.3 months, the median survival was 17.9 months and the two and five-year survival rates were 36 and 19%. The, treatment was generally well tolerated during both the induction G and the GRT. Episodes of Gr 3/4 toxicity on GRT (n=55): leukopenia - 10/0, lympho-penia - 8/13, neutropenia - 8/0, thrombocytopenia 4/0, fatigue 9/0, pain 5/0, nausea/vomiting 8/0. Episodes of Gr 3/4 toxicity on induction G (n=35): leukopenia - 1/0, lymphopenia - 1/0, neutropenia 5/3, fatigue - 1/0, pain - 5/1, nausea/vomiting - 1/0. Conclusion: Survival for both LA and HR patients with this concurrent gemcitabine radiotherapy regimen is promising and warrants further investigation. 64 Phase I Study of Stereotactic Radiotherapy for Unresectable Primary and Metastatic Liver Cancer L. Dawson, M. Hawkins, C. Eccles, T. Craig, J-P. Bissonnette, G. Lockwood, J. Zhang, J. Kim, B. Cummings, M. Sherman, J. Knox, S. Gallinger Princess Margaret Hospital, University of Toronto, Toronto, Ontario laura, dawson~rmp, uhn. on. ca
Purpose: To report results of a Phase I study of highly individualized, stereotactic radiotherapy (SRT) in unresectable liver cancer. M e t h o d s : Eligible patients had unresectable or medically inoperable hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC) and liver metastases (LM), liver enzymes <6 fold higher than normal and Child score A. Patients were stratified based on diagnosis (primary, metastatic) and effective liver volume irradiated (low <20%, mid 20-50%, high 50-80%). Patients were treated with breath hold if feasible and daily image guidance. SRT was delivered in six fractions. The dose was individualized to maintain the same nominal estimated risk of classic radiation-induced liver disease (RILD) at three levels (I - 5% risk, II - 10% risk, I l I - 20%, maximum dose 60 Gy). Results: From August 2003 to March 2006, 82 maximally pretreated patients initiated SRT. Three patients discontinued treatment early due to a variceal bleed (HCC), sepsis (CC) and progressive disease (LM). Seventy-nine patients completed SRT (34 LM, 33 HCC, 12 CC). The median age was 64 years (38-92 years). The median tumour volume was 293 cc (2.9-3088 cc).
September 13-16
58 Identification of Predictive Factors of Response to Radiation Therapy in Patients with Carcinoma of the Cervix C. Doll1, P. Craighead I, S. Lees-Miller 2, D. Demetrick 2, T. Magliocco 2 Torn Baker Cancer Centre, University of Calgary, Calgary, AIbertal ; University of Calgary, Calgary, Alberta 2 corinned@cancerboard, ab. ca
Purpose: To identify predictive factors for tumour response after radiation therapy in patients with carcinoma of the cervix, and to correlate the tumour expression of molecular markers with local control, disease-free and overall survival. Materials and Methods: This is a retrospective study of patients who completed radical radiotherapy alone for cervix cancer between 1986 and 1996. One hundred and ninety-two patients were identified. Patient and turnout data, as well as treatment parameters and outcomes, were obtained from patient records. One hundred and four patients had pretreatment tumour specimens available for analysis. Tissue microarrays were constructed from these tumour blocks. Immunohistochemica~ assays were performed with marker expression determined independently by two physicians blinded to clinical outcome. To date, immunostaining has been performed for detection of COX-2, GLUT-l, EGFR, involucrin, p53, and c-erbB-2 expression. Further immunostaining on hypoxia markers, as well as DNA repair markers, is underway. For analysis purposes, samples will be divided into radiosensitive and radioresistant groups based on clinical response, and differences in marker expression will be investigated. Results: Median follow-up was eight years. Mean patient age was 54 years, and median clinical tumour size was 5cm. The majority of patients (78%) had Stage I or II disease. Mean radiation dose to point A was 8165 cGy. Pelvic recurrence occurred in 28% of patients, with a median time to recurrence of 16 months. Distant metastases were seen in 18% of patients. Positive immunostainlng for GLUT-1 was seen in 90% of tumour specimens, COX-2 positive staining in 85%, EGFR positive staining in 67%, and p53 positive staining in 18% of specimens. Only 0.5% of tumour specimens stained positive for c-erbB-2 expression. We are currently analyzing expression profiling with clinical outcome parameters, results of which will be available for presentation. 59 Development of a Three-Dimensional Anisotropic Pelvic Lymph Node Clinical Target Volume Using Magnetic Resonance Lymphography with Ferumoxtran-lO R. Dinniwell, P. Chan, M. Haider, A. Fyles, M. Milosevic Princess Margaret Hospital, University of Toronto, Toronto, Ontario Rob. Dinniwell@rm p. uhn. on. ca
Purpose: To develop three-dimensional anisotropic scale factors for the use of the pelvic vasculature as a surrogate for lymphatic target volume definition using Magnetic Resonance Imaging (MRI) with an ultra-small superparamagnetic iron oxide that delineates phagocytotic activity within lymph nodes. Methods: A single centre trial was undertaken in patients with genitourinary and gynaecological malignancies. All patients underwent pre- and post- contrast MRI studies over two consecutive days. Ferumoxtran-10 (Combidex(r): Advanced Magnetics, Inc, Cambridge, MA) was administered on the first day. Axial images were obtained at 3mm intervals through the pelvis. Lymph node frequency and location relative to the adjacent vascular segments was analyzed. Each lymph node was divided into 0.5 x 0.5 x 3mm 3 nodal voxels. The radial position and minimal distance between the centre of each nodal voxel and the closest artery or vein (in three-dimensions) was calculated. Results: Twenty-five patients have been analyzed. A mean of 24 lymph nodes (range 18 to 34) were identified per patient. The maximum distance of the lymph nodes from the closest vessel was between 2.5 and 30ram, with a mean distance of
CARO 2 0 0 6
7.5mm. Anisotropic margins with radial divisions of 60 and 90 degrees revealed significant differences in the anterior, posterior, medial and lateral distribution of the lymph nodes along each of the pelvic vascular segments. The nodal volumes were distributed with: 47% anterior, 11% posterior, 17% medial and 25% lateral to the common lilac vessels; 19% anterior, 32% posterior, 23% medial and 26% lateral to the external lilac vessels; and 38% anterior, 7% posterior, 34% medial and 21% lateral to the internal lilac vessels. Conclusions: The development of anisotropic scale factors specific to the pelvic vasculature and the adjacent lymphatics will facilitate improved coverage of the critical lymph node targets using their corresponding vascular segments as surrogates. 6O Improving Image-Guided Target Localization through Deformable Registration K. Brock, M. Hawkins, C. Eccles, J. Moseley, D. Moseley, L. Dawson Princess Margaret Hospital, University of Toronto, Toronto, Ontario kristy, brock@rinD, uh n. on. ca
Purpose: To quantify the improvements in online target localization using deformable image registration and kV conebeam CT (CBCT). Methods and Materials: Twelve patients treated under a Research Ethics Board approved hypo-fractionated liver protocol were imaged using CBCT at each of the six treatment fractions. The images were imported into the treatment planning software and aligned, using rigid registration, to best fit the liver into the contours previously drawn on the CT scan. The liver was then contoured on each CBCT image. Deformable registration was performed to align the liver, defined'on the CT image, to each CBCT image, using MORFEUS, a biomechanical model based deformable image registration algorithm. The tumour, defined on the planning CT, was mapped onto the CBCT, through the deformable registration, which accounts for the biomechanical relationship between the liver and the tumour. The displacement of the centre of mass (COMT) of the turnout was computed. Results: The mean (SD) displacement of the COMT following deformable registration across all 12 patients was -0.03 (0.10), -0.01 (0.16), and -0.02 (0.14) cm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The maximum displacement of the COMT was 0.36, 0.65, and 0.57cm in the LR, AP, and SI directions, respectively. Ten percent of the treatment fractions had a COMT displacement of greater than 3mm in one direction and 33% of patients had at least one fraction with a displacement of greater than 3ram. COMT displacement loosely correlated with mean liver deformation (R2 = 0.30, 0.51, and 0.13 in the LR, AP, and SI directions, respectively). Conclusions: Rigid registration of the liver volume between CT and CBCT localizes the tumour to within 3mm for the majority (66%) of patients; however, larger offsets in tumour can be observed if liver deformation is evident during rigid registration. 61 Late Toxicity After Adjuvant Radiochemotherapy for Gastric Adenocarcinoma B. Wysocka, Z. Kassam, G. Lockwood, J. Brierley, L. Dawson, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wvsocka@rmD. uhn. on. ca
Purpose: To assess late toxicity following adjuvant therapy for resected gastric cancer. Methods: A retrospective review of radiation dose volume histograms (DVHs) for liver and kidneys and of late toxicity (clinical or biochemical) was performed for gastric cancer patients who received adjuvant radiochemotherapy between 2000 and 2005.
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Results: The records of 80 patients were reviewed. The mean age was 58 years (range 22-75), with 53 (66%) males. Stage distribution was: IB - 13 (16%), II - 32 (40%), I I I A - 24 (30%), IIIB - 4 (9%) and IV - 7 (9%). 45 Gy in 25 fractions was delivered with a conformal technique. Bolus 5FU and folinic acid was given in 69; 11 received investigational 5FU and Cisplatin in escalating dose. All treatment was completed in 56 (70%) patients; nine (11%) did not complete radiotherapy and 22 (27.5 %) had chemotherapy dose omissions. Median follow up is 30 months (range 6-62). At two years, overall survival was 84% (95% CI 73%-90%). Mean V30 (volume receiving 30 Gy or more) for liver was 31%, whereas mean V22.5 was 31%, 18% and 25% for left kidney, right kidney and combined volume of both kidneys, respectively. Mean of means was 22 Gy for liver and 15 Gy for kidneys. Late toxicity occurred in six patients at nine to 53 months following treatment: bowel obstruction/ perforation (2) and anastomotic stricture (4), in volumes treated to 45 Gy. There was no clinical renal or hepatic toxicity. Grade 1 (CTCAE v3.0) creatinine elevation was observed in eight (10%) patients; at least one liver test was altered in 22 (27.5%): grade 1-17; 2-4; 3-1. Abnormal bloodwork occurred nine days to 55 months after treatment and did not correlate with higher kidney and liver doses. Conclusions: In our cohort of patients treated with radiochemotherapy, small bowel and anastomotic toxicity prevailed, with no clinical renal or hepatic toxicity observed. Biochemical renal and hepatic changes were not related to clinical toxicity or dose delivered. 62 Upper Abdominal Organ Motion During Conformal Radiotherapy for Gastric Carcinoma B. Wysocka, Z. Kassam, G. Lockwood, L. Dawson, J. Brierley, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wysocka@rmp. uh n. on. ca
Aim: To determine respiratory and interfraction organ motion in gastric cancer patients receiving adjuvant radiochemotherapy. Methods: Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained on 17 patients in weeks one, three and five of post-operative gastric cancer treatment with BodyFix immobilization. Images from 138 scans were registered to the planning CT using automated bone registration. Volumes of interest (VOI) were contoured [right (RK) and left (LK) kidney, liver (L), stomach (S), pancreas (P), celiac axis (C) and porta-hepatis (PH) and the centre of mass of each organ was identified as a point of interest (POI). POIs were also placed at dome of diaphragm (D) and splenic hilum (SH). Organ motion was measured using the difference of POI position in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Inhale and exhale positions at each time point were used to determine respiratory motion. Interfractional motion at weeks one, three and five was determined and compared to planning (FB) or week one (I, E) scan. Results: Respiratory motion is maximal in the CC direction with median absolute displacements of: SH 24, LK 20.8/RK 19.6, D 20.5, L 16.1, S 15.5, P 15.1, PH 12 and C 3.Smm. In the AP direction, the greatest median displacement was: SH 9.4ram and in the RL direction motion was less (maximal for PH and SH, 2.9ram). Median absolute respiratory displacement for all organs was: 17.5mm CC, 5.9mm AP, and 2.7ram RL. Median interfraction displacement (range, mm) for all organs was: CC 4.6 (0-38), AP 2.2 (0-20.5), RL 2.2 (0-37.1) in FB; CC 6.3 (0-36), AP 3.8 (0.1-16.6), RL 2.5 (0-19.6) in I and CC 6 (046), RL 2.6 (0-19.4), AP 2.3 (0-12.9) in E. Conclusions: 1) Organ motion in upper abdomen can be substantial and should be incorporated in the planning target volume for conformal or IMRT planning. 2) Median interfraction organ position variability is substantial and similar for all phases of breathing.
September 13-16
$19
63 Primary and Adjuvant Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase I / I I Study with Long Term Outcome A.M. Brade, C. Townsley, C. Brezden-Masley, D. Hedley, M. MacLean, S. Gallinger, G, Pond, A.M. Oza, M.J. Moore, J. Brierley Princess Margaret Hospital, University of Toronto, Toronto, Ontario anthony, brade@rm p. uhn. on. ca
Objectives: Gemcitabine (G) is active against pancreatic carcinoma and is a potent radiosensitizer. We present extended follow-up data from a Phase I/II study of patients treated with combination Gemcitabine and radiation (GRT). Methods: Eligible patients had either LA or high risk resected (R) pancreatic cancer (positive nodes or positive margin). Twenty-eight were enrolled in a Phase I study of increasing doses of radiotherapy (35 Gy [n=7]/43.75 Gy [n=11]/52.5 Gy (n=10) given over 4, 5 or 6 weeks, respectively in 1.75 Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently 35 were treated with induction G 1000 rag/m2 7/8 weeks followed by concurrent bi-weekly Gemcitabine (40 mg/m2) with 52.5 Gy (30 fractions of 1.75 Gy over six weeks). In total there were 63 patients (30 LA and 33 R) treated between March 1999 - July 2001. Results: In the LA population the best response observed was CR - 1, PR - 2, SD - 10, PD - 10. GRT was not delivered to eight patients due to progression on G alone (n=5) or patient request (n=3). By intent to treat analysis, the median survival in LA disease was 14.5 months and two-year survival was 17%. In the resected population the median time to progression was 8.3 months, the median survival was 17.9 months and the two and five-year survival rates were 36 and 19%. The, treatment was generally well tolerated during both the induction G and the GRT. Episodes of Gr 3/4 toxicity on GRT (n=55): leukopenia - 10/0, lympho-penia - 8/13, neutropenia - 8/0, thrombocytopenia 4/0, fatigue 9/0, pain 5/0, nausea/vomiting 8/0. Episodes of Gr 3/4 toxicity on induction G (n=35): leukopenia - 1/0, lymphopenia - 1/0, neutropenia 5/3, fatigue - 1/0, pain - 5/1, nausea/vomiting - 1/0. Conclusion: Survival for both LA and HR patients with this concurrent gemcitabine radiotherapy regimen is promising and warrants further investigation. 64 Phase I Study of Stereotactic Radiotherapy for Unresectable Primary and Metastatic Liver Cancer L. Dawson, M. Hawkins, C. Eccles, T. Craig, J-P. Bissonnette, G. Lockwood, J. Zhang, J. Kim, B. Cummings, M. Sherman, J. Knox, S. Gallinger Princess Margaret Hospital, University of Toronto, Toronto, Ontario laura, dawson~rmp, uhn. on. ca
Purpose: To report results of a Phase I study of highly individualized, stereotactic radiotherapy (SRT) in unresectable liver cancer. M e t h o d s : Eligible patients had unresectable or medically inoperable hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC) and liver metastases (LM), liver enzymes <6 fold higher than normal and Child score A. Patients were stratified based on diagnosis (primary, metastatic) and effective liver volume irradiated (low <20%, mid 20-50%, high 50-80%). Patients were treated with breath hold if feasible and daily image guidance. SRT was delivered in six fractions. The dose was individualized to maintain the same nominal estimated risk of classic radiation-induced liver disease (RILD) at three levels (I - 5% risk, II - 10% risk, I l I - 20%, maximum dose 60 Gy). Results: From August 2003 to March 2006, 82 maximally pretreated patients initiated SRT. Three patients discontinued treatment early due to a variceal bleed (HCC), sepsis (CC) and progressive disease (LM). Seventy-nine patients completed SRT (34 LM, 33 HCC, 12 CC). The median age was 64 years (38-92 years). The median tumour volume was 293 cc (2.9-3088 cc).